The Gram-positive bacterium Streptococcus pneumoniae is a major cause of disease, suffering and death worldwide. Diseases caused by infection with this agent include otitis media, pneumonia, bacteremia, sepsis and meningitis. In some cases, infected individuals may become asymptomatic carriers of S. pneumoniae, thereby readily allowing the rapid spread of this infective agent throughout the population. In view of the serious consequences of infection with S. pneumoniae, as well as its rapid spread within and between populations, there is an urgent need for safe, effective vaccination regimes. Current methods of vaccination are based on inoculation of the subject with polysaccharides obtained from the capsules of S. pneumoniae. While these polysaccharide-based vaccine preparations have been found to be reasonably efficacious when used to prevent infection in adult populations, they are significantly less useful in the treatment of young children (under two years of age) and the elderly. One commonly-used capsular polysaccharide 23-valent vaccine, for example, has been found to be only 60% effective in preventing S. pneumoniae invasive disease in elderly subjects and completely incapable of yielding neither long-term memory (Hammitt, et al., 2011, Vaccine 29: 2287-2295) nor clinically-useful antibody responses in the under-two age group (Shapiro E. D. et al., 1991, N. Engl. J. Med. 325: 1453-1460).
In an attempt to increase the immunogenicity of these vaccines, various compositions comprising capsular polysaccharides that have been conjugated with various carrier proteins and combined with adjuvant have been used. The resulting so-called conjugate vaccines (CV) currently include 10-13 serotypes. Although vaccines of this type constitute an improvement in relation to the un-conjugated polysaccharide vaccines, they have not overcome the problem of coverage, since they are effective against only about 10% of the 92 known capsular serotypes. Consequently, upon vaccination, pneumococcal carriage and repopulation with serotypes not present in the vaccine occurs (Dagan, 2009, Vaccine 27 Suppl 3: C22-24).
In the cases of certain other bacteria of pathogenic importance for human and other mammalian species, vaccines comprising immunogenic virulence proteins are currently being developed. Such protein-based vaccines should be of particular value in the case of vulnerable subjects such as very young children, in view of the fact that such subjects are able to produce antibodies against foreign proteins. Unfortunately, very little is known of the molecular details of the life cycle of S. pneumoniae, or of the nature of role of the various virulence factors which are known or thought to be involved in targeting and infection of susceptible hosts.
Several publications describe and characterize specific S. pneumoniae proteins. For example, U.S. Pat. No. 5,958,734, U.S. Pat. No. 5,976,840, U.S. Pat. No. 6,165,760 and U.S. Pat. No. 6,300,119 disclose S. pneumoniae GtS polypeptides of various lengths, polynucleotides encoding them and methods for producing such polypeptides by recombinant techniques. WO 02/077021 the sequences of about 2,500 S. pneumoniae genes and their corresponding amino acid sequences from type 4 strain that were identified in silico. U.S. Pat. No. 6,699,703 and its counterparts discloses about 2600 S. pneumoniae polypeptides and methods for producing such polypeptides by recombinant techniques, compositions comprising same and methods of use in the preparation of a vaccine. WO 98/23631 relates to 111 Streptococcal polynucleotides identified as having a GUG start codon, which encodes a Val residue, to polypeptides encoded by such polynucleotides, and to their production and uses. WO 02/083833 discloses 376 S. pneumoniae polypeptide antigens which are surface localized, membrane associated, secreted or exposed on the bacteria, for preparation of a diagnostic kit and or vaccine. Although suggested in part of the publications, no working examples for the use of the proteins as antigens in the production of a vaccine were provided. Furthermore, none of these references disclose or suggest that use of selected protein antigens which do no elicit immune response in infants and in elderly, improve the outcome of vaccination against S. pneumoniae. 
Phosphoenolpyruvate protein phosphotransferase (PPP, also known as PtsA) is an intracellular protein that belongs to the sugar phosphotransferase system (PTS) and is also localized to the bacterial cell wall. In the cytoplasm PPP belongs to the group of phosphtransferase systems (PTS) responsible for carbohydrate internalization, which occurs concurrently with their phosphorylation. The phosphorylation of the membrane-spanning enzyme is dependent upon a group of proteins that sequentially transfer a phosphate group to this enzyme. PPP is a cytoplasmic protein that catalyzes the initial step in this process by transferring a phosphate group from phosphoenolpyruvate to a histidine in another enzyme, HrP in this system (Saier, M. H., Jr. & Reizer, J. 1992, J Bacteriol 174: 1433-1438).
There is an unmet need to provide protein-based vaccine compositions which overcome the problems and drawbacks of currently available vaccines, by being effective against a wide range of different S. pneumoniae serotypes, and capable of protecting all age groups including infants and elderly.